Spatio-molecular gene expression reflects dorsal anterior cingulate cortex structure and function in the human brain

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• The dorsal anterior cingulate cortex (dACC) is crucial for cognitive control, reward processing, and emotional regulation.
• Dysfunction in the dACC is linked to neuropsychiatric disorders.
• The dACC is an evolutionarily older brain region with unique cell types like von Economo neurons (VENs).

Purpose of the Study:

• To define molecular profiles and spatial domains of dACC cell types.
• To investigate the spatio-molecular specializations and evolution of the dACC compared to the dorsolateral prefrontal cortex (dlPFC).
• To provide a comprehensive molecular resource for the scientific community.

Main Methods:

• Paired spatially-resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) were performed on human dACC tissue.
• Non-negative matrix factorization (NMF) integrated snRNA-seq and SRT data to infer spatial localization of gene expression patterns.
• Cross-region comparison with dlPFC data analyzed spatio-molecular specializations and laminar organization.

Main Results:

• Defined molecular profiles and spatial topography for dACC cell types, including VENs.
• Identified enrichment of disease risk and putative connectivity for spatially-localized dACC cells.
• Revealed spatio-molecular differences and laminar organization between dACC and dlPFC.

Conclusions:

• This study provides a high-resolution molecular atlas of the human dACC.
• The findings offer insights into dACC function, evolution, and its role in neuropsychiatric disorders.
• Raw and processed data are publicly available to facilitate further research.